Process improvements for preparing catheter balloons

ABSTRACT

A method for forming a balloon for a dilatation catheter may utilize the steps of extruding a tubing preform of a polyester resin and then blowing the tubing into an oriented balloon, wherein the tubing preform is dried prior to blowing into the balloon form. Other process steps by which balloon cone and waist thicknesses may be reduced involve varying the axial tension and blowing pressure at several stages as a mold containing the balloon preform is dipped into a heating medium. Specifically, tubing of a thermoplastic material is placed in a mold and blown by pressurizing and tensioning the tubing and gradually dipping the mold into a heated heat transfer media so as to sequentially blow a first waist, a body and a second waist portion. The tubing is subjected to a relatively lower pressure while the body portion is blown than while the first and second waist portions are blown.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.08/197,634, filed Feb. 17, 1994, now abandoned, which is acontinuation-in-part of U.S. patent application Ser. No. 08/124,238,filed Sep. 20, 1993, now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to a method for making balloons forcatheters used in medical dilatation procedures.

Balloon catheters are being used extensively in procedures related tothe treatment of blood vessels. For example, arterial stenosis iscommonly treated by angioplasty procedures which involve insertingballoon catheters into specific arteries. Balloon catheters have alsobeen found useful in procedures involving dilation of body cavities.

The most widely used form of angioplasty makes use of a dilatationcatheter which has an inflatable balloon at its distal end. Usingfluoroscopy, a physician guides the catheter through the vascular systemuntil the balloon is positioned across the stenoses. The balloon is theninflated by supplying liquid under pressure through an inflation tureento the balloon. The inflation of the balloon causes stretching of ablood vessel and pressing of the lesion into the blood vessel wall toreestablish acceptable blood flow through the blood vessel.

In order to treat very tight stenoses with small openings, there hasbeen a continuing effort to reduce the profile of the catheter so thatthe catheter can reach and pass through the small opening of thestenoses. There has also been an effort to reduce the profile of thecatheter after an initial use and deflation of the balloon to permitpassage of the catheter through additional lesions that are to betreated or to allow entry and retreatment of lesions that reclose afterinitial treatment.

One factor manipulated to reduce the profile of the dilatation catheteris the wall thickness of the balloon material. Balloons for dilatationballoon catheters have been made from a wide variety of polymericmaterials. Typically the balloon wall thicknesses have been on the orderof 0.0004 to 0.003 inches for most materials. There have been continuingefforts, however, to develop ever thinner walled balloon materials,while still retaining the necessary distensibility and burst pressurerating, so as to permit lower deflated profiles.

It is possible to make balloons from a variety of materials that aregenerally of the thermoplastic polymeric type. Such materials mayinclude: polyethylenes and ionomers, ethylene-butylene-styrene blockcopolymers blended with low molecular weight polystyrene and,optionally, polypropylene, and similar compositions substitutingbutadiene or isoprene in place of the ethylene and butylene; poly(vinylchloride); polyurethanes; copolyesters; thermoplastic rubbers;silicone-polycarbonate copolymers; polyamides; and ethylene-vinylacetate copolymers. Orientable polyesters, especially polyethyleneterephthalate (PET), are among the preferred materials for formingcatheter balloons.

References illustrating the materials and methods of making catheterballoons include: U.S. Pat. No. 4,413,989 and U.S. Pat. No. 4,456,000 toSchjeldahl et al, U.S. Pat. Nos. Re 32,993 and Re 33,561 to Levy, andU.S. Pat. No. 4,906,244, U.S. Pat. No. 5,108,412 and U.S. Pat. No.5,156,612 to Pinchuck et al. The Levy patents, teach that a high tensilestrength polyethylene terephthalate balloon can only be formed from ahigh intrinsic viscosity polymer, specifically, high molecular weightpolyethylene terephthalate having a requisite intrinsic viscosity of atleast 1.0.

High tensile strengths are important in angioplasty balloons becausethey allow for the use of high pressure in a balloon having a relativelysmall wall thickness. High pressure is often needed to treat some formsof stenosis. Small wall thicknesses enable the deflated balloon toremain narrow, making it easier to advance the balloon through thearterial system.

Polyesters possessing a lower intrinsic viscosity are easier to process,and hence balloon manufacturers have desired to use polyesterspossessing an intrinsic viscosity below 1.0. However, it was thoughtthat using such material would sacrifice the strength of the balloon.Recently it has been discovered that angioplasty catheter balloons,having a wall strength of greater than 30,000 psi and a burst strengthof greater than 300 psi, can be prepared from a PET polymer of anintrinsic viscosity of 0.64-0.8. This, high strength, non-compliantballoon, made from a standard intrinsic viscosity polyester, has been asignificant improvement in the art. There remains, however, a need tocontinue to improve balloon wall strengths while simultaneously reducingtheir wall thickness.

Prior art PET balloon forming techniques involve blowing or stretchingand blowing of the balloon in a segment of extruded PET tubing. It hasbeen recognized that control of moisture in the PET resin, prior toextrusion, is important and prior art techniques have embodied a dryingstep prior to extrusion of PET tubing from which the balloon is formedby stretch blow molding techniques. However it has not been previouslysuggested that drying of extruded tubing would provide any benefitproperties of the balloons produced from the extruded tubing.

Balloons produced by stretching and blowing a tubular preform or"parison" typically have much thicker waist and cone walls than the wallthickness of their body portions. The thicker cone walls contribute tothe overall thickness of the catheter, making tracking, crossing andrecrossing of lesions more difficult. Further, thick cones interferewith refolding of the balloon on deflation so that the deflated ballooncan only be further inserted or withdrawn with difficulty, occasionallyeven damaging the blood vessel.

There have been several solutions proposed for reducing the cone orwaist thickness of catheter balloons in U.S. Pat. No. 4,906,241, U.S.Pat. No. 4,963,313, and EP 485,903. However, the procedures involved inthese references are quite cumbersome and so it is desirable thatsimplified methods be developed to provide cone and waist walls withreduced thicknesses.

SUMMARY OF THE INVENTION

The present invention in one aspect is an improved method for forming aballoon for a dilatation catheter involving the steps of extruding atubing preform of a polyester resin and then blowing the tubing into anoriented balloon, the improvement comprising that the tubing preform isdried prior to blowing into the balloon form. The addition of this novelstep to the balloon forming method has been observed to cause areduction in the frequency of balloons which are rejected because ofdefects in the balloon wall while producing the same or higher wallstrengths in the non-defective balloons obtained.

It has also been discovered that the problem of thick balloon cones andwaists can be substantially improved by varying the axial tension andblowing pressure at several stages as a mold containing the balloonpreform is dipped into a heating medium. A further aspect of theinvention therefore is an improved method of forming a balloon for acatheter, comprising placing tubing of a thermoplastic material in amold and blowing the balloon by pressurizing and tensioning the tubingand gradually dipping the mold into a heated heat transfer media so asto sequentially blow the first waist, the body and the second waistportions of the balloon, the tubing being subjected to a relativelylower pressure, and preferably a relatively a lower tension, while thebody portion is blown than while the first and second waist portions areblown.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an angioplasty catheter having a balloonof the invention mounted thereon.

FIGS. 2a, 2b and 2c illustrate the results of various process steps informing a catheter balloon, depicting respectively, side elevationalviews of an extruded tube of polymer material used to form the balloon,a stretched tubing preform prepared from the extruded tube, and a formedballoon prepared from the stretched tubing preform.

FIG. 3 is a schematic view of a stretching device that may be useful inpracticing the method of the invention.

FIG. 4 is a cross-sectional view of a preferred mold used in the methodof the invention.

FIG. 5 is a side elevation view of a molding station that may be usefulin practicing the method of the invention.

FIG. 6 is a perspective schematic representation of relevant portions ofthe molding station of FIG. 5.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A dilatation balloon catheter of the present invention, illustratedgenerally at 10 in FIG. 1, includes an inflatable balloon 14 mounted atthe distal end of an elongated flexible shaft 11. Catheter 10 isconventional in its construction, providing a lumen communicating withthe interior of balloon 14, for inflation and deflation of the balloon,and other optional features conventional in the dilatation catheter art.The balloon 14 is in its inflated configuration. The balloon 14 isformed of a thermoplastic polymer material which provides the balloonwith its essential compliance characteristics. The balloon may benoncompliant and made of stiff materials such as PET or nylon, or it maybe compliant, made of polyester copolymers, blends of polyesters orblends of a polyester with a minor portion of another thermoplasticpolymer which disrupts the crystallinity of the polyester. Otherthermoplastic materials such as previously described for catheterballoons may be employed. Most advantageously the balloon material is apolyester; a polyamide or similar highly orientable polymer material.

The balloon of this invention, in one aspect, is obtained by extrudingtubing of a thermoplastic polymer comprising a polyester, drying thetubing, suitably for at least 4 hours, and preferably at least 24 hours,and then expanding the extruded tubing axially and radially. In thisdrying step the tubing is suitably dried to a moisture content weight of0.15% or less, by any suitable means, including vacuum drying with orwithout heat and with or without a desiccant.

Any conventional extruder may be employed to perform the extrusionprocess. After the resin has been extruded into tube form and dried, itpreferably undergoes a prestretch which axially elongates the tubing.Referring to FIGS. 2a-2c, the prestretching process comprises applyingan axial stretching force to the extruded tubing 12, heating theextruded tubing, allowing the extruded tubing to stretch whilemaintaining the axial stretching force and finally cooling the stretchedtubing 13. Once the prestretch is complete, the stretched tubing 13 isradially expanded into the form of a balloon 14, using a moldingprocess. The molding process comprises placing the stretched tubing 13in a mold, heating the mold and expanding the stretched tubing radiallyby means of internal pressure. After sufficient time has passed for theballoon to form, the mold is cooled and the balloon 14 is removed.

The starting resin used to produce the balloon of this invention is mostpreferably a PET homopolymer or copolymer. The resin should berelatively free of foreign material and other contaminants. Polyethyleneterephthalate in pellet form may be employed. Suitable examples areShell Chemical's "Cleartuf 7207" and "Traytuf 7357", and DuPont's "SelarX260". The intrinsic viscosity of the PET resin is preferably between0.64-0.80, more preferably between 0.68-0.76 and most preferably between0.72-0.74. Intrinsic viscosity, which is a function of the molecularweight, may be determined by means of manufacturer standard processes,or ANSI/ASTM D 2857-70.

Well controlled processing of the PET resin is important to attainingthe desired strength and compliance characteristics in the finalballoon. The PET resin is preferably dried to less than 10 ppm moisturecontent prior to extrusion. Drying to this level prevents excessivedegradation of the material during extrusion and also reduces otherdefects such as tubing haziness or bubbles.

Once the pellets have been sufficiently dried, they are extruded undercarefully controlled conditions. As stated previously, any conventionalextruder may be employed to perform the extrusion. Suitably, a Killionextruder with a 1.25 inch diameter barrier flight screw is used.

In order to obtain optimal results, the processing temperatures appliedto transform the raw resin into balloon preform tubing are meticulouslymaintained. A preheater may be employed that permits the use of a smallextruder while still maintaining normal torque levels. The preheaterheats the resin to 370° F. Thereafter, the pellets move to thefeedthroat which is maintained at a temperature of 140°-180° F. Next,the PET material passes through three extruder zones, the first of whichis preferably maintained at 490° F. (+/-5° F.) while the following twoare maintained at 500° F. (+/-5° F.). The PET material then passesthrough a clamp and a melt filter before it reaches the die. The clamp,melt filter and two temperature zones within the die are all maintainedat 500° F. (+/-5° F.). The melt filter removes foreign matter from thePET material, thereby ensuring a correct failure mode in the finalballoons. Optimally, the residence time in the extruder is kept to aminimum. The preferred die size is in the range of 0.060-0.080 inches.

After the PET material extrudes out of the die in tube form, it must becooled. One way to perform the cooling process is to pass the extrudedtubing from the extruder, through a small air gap and into a water bathmaintained at approximately 60°-70° F. A puller may be used to pull thetube from the cooled end through the water bath. Thereafter, the tubingis cut into lengths. The area draw down ratio of the extruded tubing(which is the area defined by the die and mandrel divided by thecross-sectional area of the extruded tubing) should be less than 10.

After the tubing has been extruded and cut, it is preferablyprestretched to axially elongate the tubing prior to its radialexpansion. In the past it was considered important to prestretch andmold the balloon soon after the tube had been extruded, to reduce thechance that the tube would not be degraded by atmospheric moisture.Immediate prestretching and blowing is sometimes inefficient in acommercial manufacturing operation, however, and was not a fullyreliable method of assuring a uniform yield of high quality balloons. Ithas now been discovered that the negative effects of exposure toatmospheric moisture can readily be avoided or reversed by desiccatingthe extruded tubing, preferably to a moisture content of no more than0.15 weight %. In accordance with one aspect of the invention,therefore, the preform is dried between the extrusion and blowing steps,suitably between extrusion and prestretching. Drying may be accomplishedby heating the extruded tubing at 50° C.-60° C. in a vacuum oven,suitably at a pressure of 10⁻⁶ aim or less; or in a desiccatorcontaining a conventional desiccant suitably at a pressure of 600-760 mmHg, at ambient temperature. The tubing is dried for a period of at least4 hours, preferably 24 hours, more preferably at least 48 hours, oruntil a sample preform of a batch introduced simultaneously into thedesiccator is measured to have a moisture content of no more than 0.15%,preferably less than 0.10%, more preferably less than 0.075%, water.Examples of suitable desiccants which may be employed to aid in dryingthe tubing include silica gel, molecular sieves, for instance molecularsieves 3A and 4A, calcium chloride, phosphorus pentoxide, and Drierite™.A combination of heat, vacuum and desiccant may be used to obtain thenecessary dryness in a shorter period of time if desired.

The prestretch step stretches a section of a cut length of tubing to apredetermined length by applying an axial stretching force to the tubewhile the tube is heated. Once the tube is exposed to the highertemperature, the axial stretching force is maintained and the tubing isstretched at a specific rate. Desirably, the tube is heated just priorto stretching.

FIG. 3 illustrates one device useful in performing the prestretch. Thedevice 18 of FIG. 3 possesses two jaws 20 and 22 capable of gripping atleast one cut length of extruded tubing 12. The stretching device 18lowers the tubing 12 into a bath 24 containing heated media maintainedat a temperature above the glass transition temperature of the extrudedtubing 12. A suitable temperature is the range extending from 85°-95° C.However, the preferred media is water at a temperature of 90° C. (+/-2°C.). The first gripping jaw 20 may remain stationary while the secondgripping jaw 22 moves horizontally at a set rate to a predeterminedfinal position, thereby achieving the desired final stretch. Thepreferred rate of stretching is 25% per second. The desired mount ofaxial elongation prior to radial expansion is in the range of 75-150%.Preferably, however, the axial elongation occurring in this phase is125%. Therefore, the stretch ratio, calculated by dividing the finallength of the stretched section of tubing (the portion between jaws 20and 22) by the initial length of that section, is 2.25.

After the tubing 12 is stretched to the desired stretch ratio andlength, it is cooled. This may be accomplished with a device such as thedevice 18 of FIG. 3 by controlling the jaws 20 and 22 such that theyfinish stretching the tubing 12 and automatically lift up out of thebath 24. The stretched tubing 13 may then be moved to a cooling waterbath (not shown), preferably maintained at room temperature. During thiscooling process, the stretched tubing portion 13 of tubing 12 is held onboth ends in order to apply sufficient tension to ensure that the tubedoes not relax and shrink or recover from the stretch.

After cooling, the stretched tubing 13 is removed from the water bathand expanded radially using internal pressure. The dimensions to whichit is stretched are preferably controlled by performing the radialstretching while the tubing 13 is in a mold having the shape of thedesired balloon. A suitable mold 28 is shown in FIG. 4. Heating thestretched tubing 13 while radially expanding it may best be accomplishedby dipping the mold 28 into hot water while internal pressure isapplied.

To perform the radial expansion step one end of the stretched tubeinside of the area where it was gripped by jaws 20 and 22 is cut off toprovide an opening to the lumen of the tubing 13. The stretched tube 13then fed through the mold 28 which consists of three parts: the proximalportion (top) 30, the body 40 and the distal (bottom) portion 50. Thesethree sections fit tightly together and provide the tubing 13 a form toblow to.

Referring to FIG. 4, the distal portion 50 of the preferred mold 28 isgenerally between 0.6 and 1.4 inches long, which includes the enlargedend section 51 used to hold the mold 28 in the molding fixture 62 (FIG.5). The distal cone section 52 is formed at an angle of between 15° and45° with the axis of the mold 28. The cup 54 of the distal portion,which interfaces with the distal insert portion 42 of body 40, generallyhas a length of 0.120 inches. The proximal portion 30 of the preferredmold 28 is generally between 1.1 and 2.0 inches long. The proximal conesection 32 is also formed at an angle of between 15° and 45° with theaxis of the mold 28. The cup 34 of the proximal portion interfaces withthe proximal insert portion 44, symmetrical with the distal insert moldportion 42 of body 40. The length for the balloon body 40 is generallybetween 0.4 and 2 inches long. The inner and outer diameter of the moldsections 30, 40 and 50, and the angles of each cone 32, 52 are bothdependent on the desired balloon size. The mold 28 for the balloon willbe different when producing different sized balloons, which is necessaryto meet the preference or needs of those who will perform medicaltreatments with the balloon.

The molds 28 of the present invention are preferably made of 303stainless steel with a smooth mirror finish to provide a smooth finishon the balloon surface. The surface roughness average should be in therange of 5-10 microns or less.

The appropriate mold 28, with the stretched tubing 13 inside, may beheated while pressure is applied using a device 60 such as the onedepicted in FIGS. 5 and 6. With this device 60, the mold 28 is placed ina holder 62. The tubing 13 extends out from the top of the mold 28 andis fed into a Touhy clamp 64 through which a pressurized fluid,preferably nitrogen gas, is applied to the inner lumen of the tubing 13.The tubing at the bottom of the mold 28 is clamped off such that no gascan flow through it. The pressure applied is suitably in the range of210-280 psi.

One advantage of using a device 60 is that tension may be applied to thetubing 13 during the molding phase. A string 65 trained over pulley 66(shown in FIG. 6 but deleted from FIG. 5 for sake of clarity) may beattached to a tension clamp 67 adjacent the Touhy clamp 64. The tensionclamp 67 holds the tubing 13 to apply tension to it without closing offthe flow path of pressurized fluid into tubing 13. Weights 68 attachedto the end of string 65 may thus provide tension to the tubing 13.Generally, 0-500 g of tension may be applied. Tension may be appliedduring the molding process to better control the wall thickness ofcertain areas of the balloon, primarily the waist sections. I Thetension decreases the cross sectional area of the balloon waists,thereby increasing flexibility in those regions.

The tubing 13, subjected to specific interior pressures, is then heated.As depicted by dashed lines in FIG. 5, the mold 28 is dipped into awater bath 70, suitably at a rate of 4 mm/sec., with the total processof submerging the mold 2.3 inches into the bath 70 taking approximately15 seconds. Preferably, the bath 70 is a hot water bath maintained at atemperature range of 85°-98° C., with 95° C. (+/-1° C.) being the mostpreferred temperature. Once the entire mold 28 has been submerged it isheld stationery for a period of time, suitably 40 seconds, while theballoon and waist portions yield completely and stabilize. The radialexpansion, or hoop ratio (calculated by dividing the inner diameter ofthe balloon by the inner diameter of the extruded tubing), should be inthe range of 6-8.5. However, the preferred hoop ratio is approximately8.0. A lower hoop ratio may result in compliance which is higher thandesired. A higher hoop ratio may result in preforms which will not blowout fully. During this phase of radial expansion, the tubing 13 willfurther elongate, i.e. expand further in the axial direction, such thatthe total elongation of the tubing 13 in the finished balloon body willrange from 175-275% of the length of the unstretched tubing used to formthe body of the balloon.

In accordance with a further aspect of the invention the stretchedtubing 13 is blown during a programmed dipping cycle, for dipping intohot water bath 70, during which the pressure and axial tension arevaried at several stages so that the balloon is sequentially blown fromone end to the other (proximal, body and distal, or vice versa). By thismethod, a reduced waist and cone thickness is obtained without thenecessity of introducing a separate processing operation directedspecifically to cone and waist reduction.

FIG. 4 has been labeled to show depth regions at which transitions ofpressure and/or tension occur in this aspect of the invention as mold 28is dipped into bath 70. Corresponding locations on the balloon 14 arelabeled in FIG. 1. The region B-C comprises the proximal waist portion,the region C-D comprises the proximal cone portion, the region D-Ecomprises the body portion, the region E-F comprises the distal coneportion and the region F-G comprises the distal waist portion of themold. The balloon blowing process of the invention involves the stepsof:

pressurizing the stretched tubing to a first pressure in the range of150-320 psi and applying a first tension in the range of 5-150 g;

dipping the mold to a first depth in the range of from the transition(C) from the first waist to the first cone to the transition (D) fromthe first cone to the body portion of the balloon;

reducing the pressure to a second pressure between 80 and 170 psi andsetting a second tension in the range of the first tension;

dipping the mold to a second depth in the range of from the transition(E) from the body portion to the second cone portion to the transition(F) from the second cone to the second waist;

increasing the pressure to a third pressure higher than the secondpressure and between 150 and 320 psi and increasing the tension to athird tension, higher than the first and second tensions, and then,

dipping the mold to a third depth (H) beyond the depth (G) of the secondwaist.

Although the process may be accomplished with substantially continuousdipping, it is preferred that the mold be held at each of the first,second and third depths for predetermined time intervals before changingpressure/tension parameters and moving to the next depth. Suitable holdtime intervals are between 1 and 40 seconds at the first depth, between1 and 40 seconds at the second depth and between 10 and 100 seconds atthe third depth. A typical dipping program for a PET polymer balloon,beginning at an initial depth (A) before the depth (B) of the firstwaist of the balloon, and using a 95° C. hot water bath as heatingmedia, will take a total of approximately 60-90 seconds. Typicalprograms for PET balloons are illustrated in Examples 4-9.

The third tension is suitably in the range of 50 to 700 g, and is higherthan the second tension, suitably higher than both the first and secondtensions. For balloons of 4.00 mm diameter or less, the third tensionwill usually not exceed 500 g. The second tension may be the same ordifferent from the first tension and if different will usually be lessthan the first tension. In general the tension employed at all depthswill be higher as the diameter of the balloon is increased. For balloonshaving nominal diameters of at least 2.25 mm it is preferred that thethird tension be higher than both the first and second tensions by atleast 150 grams and at all typical angioplasty balloon diameters it ispreferred that the difference between the second and third pressures beat least 100 psi, usually at least 150 psi.

It should be noted that this aspect of the invention can also bepracticed by inserting the end of mold 28 which forms the distal end ofthe balloon into the heating bath first.

The balloon formed in the mold is next cooled. One way to cool theballoon is to remove the mold 28 from the hot water bath 70 and place itin a cooling bath 72. As shown in FIG. 5, this step may be accomplishedthrough use of a machine 60 having a pivot arm 74 capable oftransferring the mold 28 from the hot 70 to the cold water bath 72. Thecooling bath 72 is preferably maintained at 7°-15° C. In the preferredembodiment, the balloon remains in the cooling bath 72 for approximately10 seconds.

Finally, the ends of the tubing 13 extending from the mold 28 are cutoff and the balloon is removed from the mold 28 by removing either thedistal end 50 or proximal end 30 from the body section 40 of mold 28,then gently pulling the balloon from the remaining mold sections. Tomount on a catheter 10, balloon 14 is cut at B and G and adhered to thecatheter in conventional manner.

The various aspects of the invention are illustrated by the followingnon-limiting examples. In the examples wall thickness measurements aresingle wall thicknesses unless specifically specified as double wallthicknesses.

EXAMPLE 1 Post Extrusion Drying

The product of this example is a 3.00 mm balloon. Shell ChemicalCleartuf 7207 PET pellets, reported as having an intrinsic viscosity of0.73 as determined by Goodyear R100E intrinsic viscosity test method,were dried to approximately 10 ppm moisture content. The dried resin wasextruded into tubing and cut into 8 inch sections. The tubing sectionshad an OD of 0.0425 in. and an ID of 0.0183 in.

The extruded tubing sections were next stretched to a predeterminedlength by applying an axial stretching force to the individual tubingsections and heating them. Each tubing section was placed in anautomated prestretching device possessing two gripping mechanismscapable of concurrent vertical motion. The prestretching device loweredthe tubing section into a deionized water bath 24 heated to 90° C. (±2°C.). One of the two gripping mechanisms remained stationary while theother moved horizontally at a rate of 25%/sec. for 5 seconds. Theresulting axial elongation, due to the 2.25 stretch ratio, wasapproximately 125%.

After the prestretch was complete, the tubing section was manuallyremoved from the pre-stretching device and cooled for a few seconds in adeionized water bath maintained at room temperature. The tubing sectionwas held in order to apply sufficient tension to ensure that the tube 12did not recover from the stretch. The stretched tubing section was thenremoved from the water bath.

After cooling, the stretched tubing section was expanded radially usinginternal pressure. One end of the stretched tube was cut to provide anopening to the lumen of the tubing. In order to form a 3.75 mm balloonwith a 20 mm body length, a mold having dimensions that allowed thestretched tube to blow out to the appropriate body size and balloonwaist inner diameters was used.

After the tubing section was securely inside the mold, the mold wasplaced in a holder. The tubing section extended out the top of the moldand was fed into a Touhy clamp through which nitrogen gas was applied tothe inner lumen of the tubing at 260 psi. No tension was applied to thetubing. The tubing section at the bottom of the mold was clamped offsuch that the pressure was maintained inside the tubing section. Themold was then gradually dipped, at a rate of 4 mm/sec., into a deionizedhot water bath maintained at 95° C. (±1° C.) to a point just above theproximal waist portion of the mold. The entire dipping process consumed15 sec. and the mold was held stationary in the bath 70 for 40 sec. Thenthe mold was removed from the hot water bath and cooled forapproximately 10 sec. in a deionized water bath maintained at about 11°C. The balloon axially expanded during the molding by an additional 50%of its original tubing length, resulting in a total axial elongation of175%.

Thirty balloons prepared in this manner from a single lot of tubing wereused as controls.

Balloons of the invention were made in the same manner from the same lotof tubing as the controls except that the prior to the prestretchingstep, the tubing sections were dried in a vacuum desiccator. Five markedand preweighed tubes were used to monitor weight loss after 24 and 48hour desiccation intervals. After 24 hours the balloons had lost anaverage of 0.38% of their undesiccated weight. After 48 hours theaverage weight loss was 0.44%.

Meanwhile, in the same desiccator, 80 unmarked tubes were dried. After24 hours 30 tubes were removed and processed into balloons in the mannerof the controls. An additional 30 balloons were made from tubes whichwere kept in the desiccator for 48 hours.

All balloons were inspected for "bubble" defects and observed defectswere categorized as small (<0.004 inch dia.), medium (0.004-0.01 inch)and large (>0.01 inch). "Bubble" defects are typically tear shaped orAmerican football shaped visible distortions which are sometimes, butnot always, hollow. Results were as follows:

Controls: 18 "bubbles". 1 Large, 7 medium, 10 small. Four balloons hadmore than one "bubble".

24 hours: 11 "bubbles". 0 Large, 1 medium, 10 small. No balloons withmore than one "bubble".

48 hours: 7 "bubbles". 0 Large, 3 medium, 4 small. No balloons with morethan one "bubble".

Six balloons from each batch which displayed no defects were thensubjected to standard burst tests by measuring the double wall thicknessof the deflated balloon, inflating the balloon at incrementallyincreasing pressures and measuring the outside diameter at eachincrement until the balloon burst. Typical and average results for eachbatch are given in Table 1 where Dnom is diameter at nominal inflation(118 psi), Pburst and Dburst are, respectively, average burst diameterand average burst pressure.

                  TABLE 1                                                         ______________________________________                                                      0 Hours    24 Hours 48 Hours                                    Single wall thickness                                                                       0.00062"   0.00067" 0.00068"                                    Pressure (psi)                                                                              Measured body diameter (mm)                                     ______________________________________                                        40            3.65       3.66     3.66                                        88            3.75       3.75     3.75                                        Dnom 118      3.79       3.78     3.78                                        132           3.80       3.79     3.79                                        147           3.82       3.80     3.80                                        180           3.84       3.83     3.82                                        206           3.86       3.84     3.84                                        235           3.89       3.86     3.86                                        260           3.92       3.88     3.87                                        270           3.95       3.90     3.88                                        280           3.98       3.92     3.90                                        290           4.01       3.93     3.92                                        300           4.05       3.95     3.93                                        310           4.10       3.98     3.96                                        320           4.14       4.00     3.99                                        330           4.21       4.04     4.02                                        340                      4.07     4.05                                        350                      4.10     4.10                                        360                      4.11     4.13                                        370                               4.18                                        Average Results                                                               Pburst        323        352      353                                         Dburst        4.13       4.11     4.09                                        Distention dnom-280                                                                         5.0%       3.7%     3.2%                                        ______________________________________                                    

EXAMPLE 2 Post Extrusion Drying

The procedures of example 1 were repeated. Average weight loss ondesiccation for 24 hours was 0.34% and for 48 hours was 0.52%. Resultsof defect inspections were as follows:

Controls: 12 "bubbles". 3 Large, 5 medium, 4 small. Three balloons hadmore than one "bubble".

24 hours: 9 "bubbles". 0 Large, 4 medium, 5 small. No balloons with morethan one "bubble".

48 hours: 5 "bubbles". 0 Large, 3 medium, 2 small. No balloons with morethan one "bubble".

Typical and average results of burst testing are shown in Table 2:

                  TABLE 2                                                         ______________________________________                                                      0 Hours    24 Hours 48 Hours                                    Single wall thickness                                                                       0.00062"   0.00067" 0.00068"                                    Pressure (psi)                                                                              Measured body diameter (mm)                                     ______________________________________                                        40            3.65       3.67     3,65                                        88            3.76       3.75     3.76                                        Dnom 118      3.79       3.78     3.79                                        132           3.81       3.79     3.80                                        147           3.82       3.80     3.81                                        180           3.85       3.82     3.83                                        206           3.87       3.84     3.85                                        235           3.90       3.86     3.87                                        260           3.94       3.88     3.89                                        270           3.97       3.90     3.91                                        280           4.01       3.91     3.92                                        290           4.04       3.93     3.94                                        300           4.08       3.95     3.96                                        310           4.13       3.98     3.98                                        320           4.15       4.01     4.01                                        330                      4.05     4.04                                        340                      4.09     4.07                                        350                      4.13     4.10                                        360                               4.12                                        Average Results                                                               Pburst        318        349      350                                         Dburst        4.13       4.12     4.12                                        Distention dnom-280                                                                         5.6%       3.4%     3.5%                                        ______________________________________                                    

EXAMPLE 3 Post Extrusion Drying

Four lots of balloons (25 in each lot) were stretched and blown fromextruded PET tubing at a mold pressure of 180 psi. The molds were for4.0 mm balloons. Mold dimensions were: length 100 mm; proximal ID0.421"; distal ID 0.0315"; body ID 0.1600". The tubing lots weresubjected to the following conditions before stretching and blowing:

A Tubing allowed to equilibrate in a dry room to a moisture content of0.3%. The stretch ratio before blowing was 2.15.

B Tubing vacuum dried to moisture content of 0.05% in a desiccator priorto stretching. The stretch ratio prior to blowing was 2.15.

C Tubing allowed to equilibrate in a dry room to a moisture content of0.3%. The stretch ratio before blowing was 2.25.

D Tubing vacuum dried to moisture content of 0.05% in a desiccator priorto stretching. The stretch ratio prior to blowing was 2.25.

In blowing each lot of stretched tubing a tension was selected to assurean axial lengthening (growth) of 17-22 mm during the blowing stage andto keep the double body wall thickness between 0.00095" and 0.00125".All balloons were inspected for "bubbles" and foreign materials. Ten ofthe best balloons from each lot were burst tested and distal andproximal waists were measured on one balloon from each lot. Blowingconditions and test results are shown in Table 3.

                  TABLE 3                                                         ______________________________________                                                   A         B        C       D                                                  Comparative                                                                             Invention                                                                              Comparative                                                                           Invention                               ______________________________________                                        Pressure (psi)                                                                           180       180      180     180                                     Tension    133       161      137     152                                     Average growth                                                                           19.7      18.9     19.2    17.5                                    (mm)                                                                          Body double wall                                                                         0.00110   0.00116  0.00108 0.00116                                 thickness (in)                                                                Small "bubbles"                                                                          3         0        2       0                                       (<0.010 mm)                                                                   Medium "bubbles"                                                                         1         0        0       0                                       (0.004-0.10 mm)                                                               Large "bubbles"                                                                          0         0        2       0                                       (>0.010 mm)                                                                   Burst diameter                                                                           4.3       4.3      4.3     4.3                                     (mm)                                                                          Burst pressure (psi)                                                                     328       336      327     337                                     Distal wall thickness                                                                    0.0037    0.0037   0.0034  0.0041                                  Proximal wall                                                                            0.0023    0.0027   0.0028  0.0026                                  thickness                                                                     ______________________________________                                    

EXAMPLE 4 Programmed Dip Cycle

Balloons were made in a manner similar to Examples 1 and 2 except that aprogrammed dip cycle was used and the device of FIG. 6 was modified byreplacing the pulley 66 and weight 68 with a metal cylinder containing apressure driven piston. String 65 was attached to the piston rod so thattension could be varied by changing the pressure in the cylinder so asto move the cylinder up or down. The program was as follows, wherepressures applied to the cylinder have been converted to equivalenttensions applied to the tubing.

    ______________________________________                                        Mold specification:                                                                          Proximal waist ID                                                                           0.0352 inches                                                   Body ID       0.1195 inches                                                   Distal waist ID                                                                             0.0280 inches                                                   Cone angle    15°                                       Prestretch stretch ratio:    2.25                                             Program:       bath at       95 °C.                                    (1)            pressure to   295 psi                                                         tension to    60 g                                                            hold at A     5 seconds                                                       dip to D      5 seconds                                                       hold at D     5 seconds                                        (2)            pressure to   120 psi                                                         tension to    60 g                                                            dip to F      10 sec                                                          hold at F     5 seconds                                        (3)            pressure to   295 psi                                                         tension to    200 g                                                           dip to G      1 sec                                                           hold at G     1 sec                                                           dip to H      10 sec                                                          hold at H     25 seconds                                       ______________________________________                                    

Average wall thickness of the balloons produced in this way were: bodysingle wall, 0.00045 inches; proximal wall, 0.00141 inches; distal wall,0.00169 inches.

In the remaining examples the modified version of the device of FIG. 6which is described in the previous example was employed and a simplifiedprogrammed dipping and blowing cycle was used. In this program the moldwas dipped from the initial position, A in FIG. 4, to a first depthapproximately at the midpoint of the first cone i.e. midway between Cand D, held and then after reducing the pressure, dipped to a seconddepth approximately at the midpoint of the second cone, i.e. between Eand F, held and then after increasing pressure and tension, dipped tothe final position H, slowing down near the final position, and thenholding for a third interval before being removed and dipped in thecooling bath.

EXAMPLE 5 Programmed Dip Cycle

2.5 mm balloons were made from 0.0125"×0.0272" PET extruded tubes. Theextruded tubes were stretched 2.25 times of the original length at 90°C. The stretched tubes were then blown into balloons at 95° C. The moldpressure was 250 psi at proximal end, 130 psi at body, 290 psi at distalend. The pulling tension was 25 grams at proximal end and body, 180grams at distal end. The dip cycle was 5 seconds hold at initialposition, 5 sec. dip to first depth, 5 sec hold at first depth; 10seconds dip to second position, 8 seconds hold at second position; 6seconds to dip to the final position, holding for 30 seconds beforeremoving and quenching in a cooling bath. The balloon has a body wall(single wall) of 0.00039", proximal waist wall of 0.0010", distal waistwall of 0.0012", pressure burst at 343 psi. The compliance at 118-279psi is less than 7%. The result is shown in Table 4.

EXAMPLE 6 Programmed Dip Cycle

3.0 mm balloons were made from 0.0149×0.0311 PET tube. Stretching andblowing temperatures were the same as example 1. The mold pressure was280 psi at proximal end, 130 psi at body, 290 psi at distal end. Thepulling tension was 50 grams at proximal end and 35 grams at body, 250grams at distal end. The dip cycle was as in Example 5. The balloon hasa body wall of 0.00040", proximal waist wall of 0.0010", distal waistwall of 0.0011", pressure burst at 320 psi. The compliance at 118-279psi was less than 7%. The result is shown in Table 4.

EXAMPLE 7 Programmed Dip Cycle

4.0 mm balloons were made from 0.0195×0.0395" PET tube. Stretching andblowing temperatures were the same as example 1. The mold pressure was280 psi at proximal end, 130 psi at body, 290 psi at distal end. Thepulling tension was 90 grams at proximal end and 90 grams at body, 350grams at distal end. The dip cycle was as in Example 5. The balloon hasa body wall of 0.00046", proximal waist wall of 0.0022", distal waistwall of 0.0023", pressure burst at 295 psi. The compliance at 118-279psi was less than 7%. The result is shown in Table 4.

                  TABLE 4                                                         ______________________________________                                                      Comparative                                                                              Invention                                                          Balloon*   Balloon  % Reduction                                 ______________________________________                                        Size: 2.5 mm                                                                  Balloon wall/inch                                                                           .00056"    .00039"  30                                          Distal waist wall                                                                           .0031"     .0012"   61                                          Prox. waist wall                                                                            .0028"     .0010"   64                                          Profile reduced**        .0038"                                               Size: 3.0 mm                                                                  Balloon wall/inch                                                                           .00056"    .00040"  29                                          Distal waist wall/inch                                                                      .0041"     .0010"   76                                          Prox. waist wall/inch                                                                       .0035"     .0011"   69                                          Profile reduced          .0062"                                               Size: 4.0 mm                                                                  Balloon wall/inch                                                                           .00062     .00046"  26                                          Distal waist wall/inch                                                                      .0051"     .0023    55                                          Prox. waist wall/inch                                                                       .0049"     .0022"   55                                          Profile reduced          .0056"                                               ______________________________________                                         *Comparative balloons were commercial balloons of comparable body             diameter and body wall thickness employed on NCShadow                         catheters sold by SciMed Life Systems Inc., Maple Grove MN, USA               and prepared by a process using constant pressure and tension.                **Profile reduced is calculated from distal waist wall thicknesses of the     comparative balloons.                                                    

EXAMPLE 8

Balloons as prepared in example 6 were mounted on catheters ofcomparable configuration to the NC-Shadow™ catheter of the same balloonbody dimension and the resulting catheters were compared for recrossingforce, pulling force, trackability and surface friendship. Recrossingforce is the force to push a deflated balloon through a 0.049 inchlesion after the balloon has been inflated to 12 atm. for 1 min. Pullingforce is the force to pull a deflated balloon catheter back through a 7Fguide catheter after balloons were inflated to 12 atm for 1 min. All ofthe measurements were done at 37° C. Results are provided in table 5.

                  TABLE 5                                                         ______________________________________                                                   Comparative                                                                   catheter                                                           ______________________________________                                                              Invention catheter                                                                        % Reduction                                 Recrossing Force                                                                         0.29       0.16        45                                          (lb)                                                                          Pulling force from                                                                       0.13       0.10        23                                          guide (lb)                                                                    Trackability          greatly improved                                        Surface friendship                                                                       rough      good                                                    ______________________________________                                    

EXAMPLE 9 Programmed Dip Cycle

3.0 mm balloons were made from 0.0149×0.0307" PET tube. The tubes weredried up to 100 ppm moisture (in the range of 10-200 ppm) beforestretching and blowing. The tube was stretched 2.15 times of theoriginal length at 90° C. The stretched tube was then blown into balloonat 95° C. The mold pressure was 270 psi at proximal end, 110 psi atbody, 270 psi at distal end. The pulling tension was 22 grams atproximal end and body, 50 grams at distal end. The dip cycle was as inExample 5. The balloon has a body wall of 0.00040", proximal waist wallof 0.0013", distal waist wall of 0.0013", pressure burst at 330 psi. Thecompliance at 118-279 psi was less than 7%.

EXAMPLE 10 Programmed Dip Cycle

3.0 mm polyethylene copolymer balloons were made from tubing having anOD of 0.032" and an ID of 0.0215". The tubes were not stretched beforeblowing. The tubes were treated with E-beams to crosslink the polymermaterial. The blowing temperature was 90° C. Mold pressure was 120 psiat both ends, 80 psi at body. Pulling tension was 500 grams at thesecond end, 0 grams at body. Balloon wall thickness of 0.0250"-0.0275"and burst pressure of 188 psi were the same as those with fixed pressureand without tension. However, the waist walls of the second ends of theresulting balloons were reduced 10-30%.

Although the present invention has been described with reference topreferred embodiments, workers skilled in the art will recognize thatchanges may be made in form and detail without departing from the spiritand scope of the invention.

What is claimed is:
 1. In a method of preparing an oriented balloon ofthermoplastic material comprising extruding a hollow tube of thethermoplastic material, and subsequently expanding the tube bysubjecting the tubing, while in a mold, to an elevated temperature andan increased interior pressure to produce an oriented balloon, theimprovement wherein the tube is subjected to a drying step, prior tosaid expanding step, thereby increasing the strength of the balloonrelative to a reference balloon prepared in the same manner, except forsaid drying step.
 2. A method as in claim 1 wherein the extruded tube issubjected to a stretching step before said expanding step and the tubeis dried before said stretching step.
 3. A method of preparing anoriented balloon as in claim 1 wherein the thermoplastic material is apolyethylene terephthalate homopolymer or copolymer.
 4. A method offorming a balloon for a catheter, the balloon having a first waistportion, a body portion and a second waist portion, the methodcomprising placing tubing of a thermoplastic material in a mold andblowing the balloon by pressurizing and tensioning the tubing whilegradually dipping the mold into a heated heat transfer media so as tosequentially blow the first waist, the body and the second waistportions of the balloon, the tubing being subjected to a relativelylower pressure while the body portion is blown than while the first andsecond waist portions are blown.
 5. A method as in claim 5 wherein thetubing is also subjected to a relatively a lower tension while the bodyportion is blown than while the first and second waist portions areblown.
 6. In a process for forming an elongated balloon having alongitudinal body portion, first and second waist portions of reduceddiameter relative to the body portion at opposite ends of the balloonand first and second cone portions connecting corresponding waistportions and respective ends of the longitudinal body portion, theprocess comprising the steps of placing an extruded and stretchedtubular preform in a mold having an internal form corresponding to thedesired outer configuration of the balloon, and forming the balloon byapplying axial tension and internal pressure to the preform upon dippingof the mold into a heated heat transfer media, the improvementcomprising that the forming step comprises:pressurizing the preform to afirst pressure in the range of 150-320 psi and applying a first tensionin the range of 5-150 g; dipping the mold to a first depth in the rangeof from the transition (C) from the first waist to the first cone to thetransition (D) from the first cone to the body portion of the balloonwhile maintaining the first tension and the first pressure, and therebyexpanding at least one portion of the preform in the mold; pressurizingthe preform to a second pressure less than the first pressure andbetween 80 and 170 psi and setting a second tension in the range of thefirst tension; dipping the mold to a second depth in the range of fromthe transition (E) from the body portion to the second cone portion tothe transition (F) from the second cone to the second waist whilemaintaining the second tension and the second pressure; pressurizing thepreform to a third pressure higher than the second pressure and between150 and 320 psi and applying to the preform a third tension, higher thanthe first tension, and then, dipping the mold to a third depth (H)beyond the depth of the second waist while maintaining the third tensionand the third pressure.
 7. A method as in claim 6 wherein the thirdtension is in the range of 50 to 700 g.
 8. In a process for forming anelongated balloon having a longitudinal body portion, first and secondwaist portions of reduced diameter relative to the body portion atopposite ends of the balloon and first and second cone portionsconnecting corresponding waist portions and respective ends of thelongitudinal body portion, the process comprising the steps of placingan extruded and stretched tubular preform in a mold having an internalform corresponding to the desired outer configuration of the balloon,and forming the balloon by applying axial tension and internal pressureto the preform upon dipping of the mold into a heated heat transfermedia, the improvement comprising that the forming stepcomprises:pressurizing the preform to a first pressure in the range of150-320 psi and applying a first tension in the range of 5-150 g;dipping the mold to a first depth in the range of from the transition(C) from the first waist to the first cone to the transition (D) fromthe first cone to the body portion of the balloon while maintaining thefirst tension and the first pressure, and thereby expanding at least oneportion of the preform in the mold; holding the mold at the first depthfor a predetermined first time interval while maintaining the firsttension and the first pressure; pressurizing the preform to a secondpressure less than the first pressure and between 80 and 170 psi andsetting a second tension in the range of the first tension; dipping themold to a second depth in the range of from the transition (E) from thebody portion to the second cone portion to the transition (F) from thesecond cone to the second waist while maintaining the second tension andthe second pressure; holding the mold at the second depth whilemaintaining the second tension and the second pressure for apredetermined second time interval; pressurizing the preform to a thirdpressure higher than the second pressure and between 150 and 320 psi andapplying to the preform a third tension, higher than the first tension;dipping the mold to a third depth (H) beyond the depth of the secondwaist while maintaining the third tension and the third pressure, andthen holding the mold at the third depth for a predetermined third timeinterval while maintaining the third tension and third pressure.
 9. Themethod as in claim 8 wherein said first time interval is between 1 and40 seconds, the second time interval is between 1 and 40 seconds and thethird time interval is between 10 and 100 seconds.
 10. The method ofclaim 8 wherein the difference between said second and third pressuresis at least 100 psi.
 11. The method of claim 8 wherein the thermoplasticmaterial is a polyethylene terephthalate homopolymer or copolymer. 12.The method of claim 11 wherein said heat transfer media is heated to atemperature of 90° C. to 100° C.
 13. The method of claim 6 wherein theextruded tubular preform is dried after being extruded and prior tobeing stretched.
 14. The method of claim 13 wherein the extruded tubularpreform is dried to a moisture content of less than 0.15 weight %. 15.The method of claim 6 wherein the second tension is the same as thefirst tension.
 16. The method of claim 6 wherein the second tension isless than the first tension.